Title: DNA damage response: three levels of DNA repair regulation.

Authors: Sirbu, Bianca M; Cortez, David

Published In Cold Spring Harb Perspect Biol, (2013 Aug)

Abstract: Genome integrity is challenged by DNA damage from both endogenous and environmental sources. This damage must be repaired to allow both RNA and DNA polymerases to accurately read and duplicate the information in the genome. Multiple repair enzymes scan the DNA for problems, remove the offending damage, and restore the DNA duplex. These repair mechanisms are regulated by DNA damage response kinases including DNA-PKcs, ATM, and ATR that are activated at DNA lesions. These kinases improve the efficiency of DNA repair by phosphorylating repair proteins to modify their activities, by initiating a complex series of changes in the local chromatin structure near the damage site, and by altering the overall cellular environment to make it more conducive to repair. In this review, we focus on these three levels of regulation to illustrate how the DNA damage kinases promote efficient repair to maintain genome integrity and prevent disease.

PubMed ID: 23813586

MeSH Terms: Ataxia Telangiectasia Mutated Proteins/metabolism*; Chromatin/genetics*; DNA Damage/physiology*; DNA Repair/genetics*; DNA Repair/physiology*; DNA-Activated Protein Kinase/metabolism*; Genomic Instability/physiology*; Models, Genetic*; Phosphorylation